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Comparative genomic analysis and clinical outcomes of BRAF-mutated advanced biliary tract cancers

PURPOSE: BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic...

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Main Authors: Tang, Tin-Yun (Author) , Nichetti, Federico (Author) , Kaplan, Ben (Author) , Lonardi, Sara (Author) , Pietrantonio, Filippo (Author) , Salvatore, Lisa (Author) , Vivaldi, Caterina (Author) , Rimassa, Lorenza (Author) , de Braud, Filippo (Author) , Rizzato, Mario Domenico (Author) , Pavlick, Dean (Author) , Chu, Randy (Author) , Danner De Armas, Anaemy (Author) , Sharaf, Radwa (Author) , Sokol, Ethan (Author) , Rodon Ahnert, Jordi (Author) , Ross, Jeffrey S. (Author) , Javle, Milind (Author) , Niger, Monica (Author)
Format: Article (Journal)
Language:English
Published: September 29, 2023
In: Clinical cancer research
Year: 2023, Volume: 29, Issue: 23, Pages: 4853-4862
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-23-1926
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-23-1926
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Author Notes:Tin-Yun Tang, Federico Nichetti, Ben Kaplan, Sara Lonardi, Filippo Pietrantonio, Lisa Salvatore, Caterina Vivaldi, Lorenza Rimassa, Filippo de Braud, Mario Domenico Rizzato, Dean Pavlick, Randy Chu, Anaemy Danner De Armas, Radwa Sharaf, Ethan Sokol, Jordi Rodon Ahnert, Jeffrey S. Ross, Milind Javle, and Monica Niger
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Summary:PURPOSE: BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC. - EXPERIMENTAL DESIGN: We analyzed two nonoverlapping cohorts. We examined the genomic landscape of BRAF-mutated iCCA in a "genomic cohort" [187 class I, 82 class II, 113 class III BRAF mutants and 8,026 wildtype (WT)]. We also analyzed median progression-free survival (PFS) and overall survival (OS) on first-line chemotherapy in a separate multi-institutional "clinical cohort" of patients with BTC (including iCCA and extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer; 41 class I, 32 class II+III BRAF mutants and 1,042 WT). - RESULTS: In the entire BTC clinical cohort, the median PFS was shorter for class I [HR, 2.11 (P < 0.001)] and class II+III [HR, 1.72 (P = 0.007)] as compared with BRAF WT. OS was also shorter in class I [HR, 2.04 (P = 0.011)] and class II+III [HR, 1.86 (P = 0.002)] as compared with BRAF WT. In the iCCA subgroup, class I alterations were mutually exclusive with FGFR2, IDH1/2, ERBB2, and KRAS mutations. Class II+III mutations appear to be mutually exclusive with FGFR2 and KRAS. - CONCLUSIONS: In BTC, all classes of BRAF mutations are associated with a worse prognosis. BRAF mutations occur in 5% of iCCA subgroup and may be mutually exclusive with other targetable mutations.
Item Description:Gesehen am 17.09.2024
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-23-1926

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